2020 Vision:
NIH Heads Foresee the Future

JAMA Medical News & Perspectives recently asked the directors of
constituents of the National Institutes of Health in Bethesda, Md, to predict
what the future portends for their disciplines.

Targeting the year 2020 because it's far enough away to allow some blue-sky
thinking yet close enough for much informed speculation, we hoped many of
the people overseeing US progress in medicine would share their thoughts on
what unfolding developments or utter surprises the first fifth of the new
century is likely to hold.

Nearly all of those we asked said they were pleased to have this opportunity to prognosticate; their responses follow.

NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE

As a result of rigorous scientific investigation, several therapeutic
and preventive modalities currently deemed elements of complementary and alternative
medicine will have proven effective. Therefore, by 2020, these interventions
will have been incorporated into conventional medical education and practice,
and the term "complementary and alternative medicine" will be superseded by
the concept of "integrative medicine."

The biological and pharmacological basis for effectiveness of selected herbal and nutritional supplements will be clarified, leading to their standardization and to the rational design of yet more potent congeners. Advances in neurobiology
will elucidate mechanisms underlying ancient practices such as acupuncture
and meditation, as well as the phenomenon of "the placebo effect."

Other modalities will have proven unsafe or ineffective, and an informed
public will have rejected them.

The field of integrative medicine will be seen as providing novel insights and tools for human health, and not as a source of intellectual and philosophical
tension that insinuates itself between and among practitioners of the healing
arts and their patients.Stephen E. Straus, MD, Director

NATIONAL EYE INSTITUTE

Thank you for your invitation to look into my crystal ball and predict
some of the areas where I believe the most significant progress will be made
in the field of vision research over the next 20 years. The first area is
that of inherited retinal degeneration. Among the diseases in this group are
retinitis pigmentosa and various forms of macular degeneration that are important
causes of blindness. I believe we will learn enough about the underlying causes
of degeneration of the photoreceptors in these diseases to develop medical
treatments that will interrupt or slow down the neurodegenerative process.

The second area of progress is related to glaucoma, a group of eye diseases
that share a distinct type of progressive damage to the optic nerve and can
lead to loss of peripheral vision and ultimately to blindness. Building on
current research findings, it is likely that new, highly effective neuroprotective
agents will be developed to safeguard the axons in the optic nerve head from
damage, thereby preventing vision loss.

Another area that has potential for significant progress is the treatment of corneal diseases. Recent studies have demonstrated that mutations in a single gene result in several types of corneal dystrophy, and several other
corneal dystrophies are currently being analyzed in genetic studies. I believe
the results from these studies will allow development of gene therapy for
some of these diseases over the next 20 years.Carl
Kupfer, MD, Director

NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Bypasses may not be passé, but they will certainly be passing
from the scene. Favorable trends in coronary risk factors should reduce the
need for intervention in many others. And even for those for whom bypass surgery
is still the best option, the results should be much more satisfactory because
the implanted vessels will behave more like arteries than veins. In fact,
they will be arteriesgrown in advance of the procedure from the patient's
own cells.Claude Lenfant, MD, Director

NATIONAL HUMAN GENOME RESEARCH INSTITUTE

In 20 years, most human diseases will be understood at the fundamental
level of molecules; knowledge about genetic control of cellular functions
will underpin future strategies to prevent or treat disease phenotypes.

In 20 years, designer drugs based on a detailed molecular understanding
of illnesses, including common illnesses like diabetes and hypertension, will
be coming on the market. For several drugs, genetic testing before prescribing
will be standard practice. In basic research, DNA sequences obtained from
numerous species will permit scientists to better understand the essential
components of cells, how cells and organisms work, and how organisms evolved
on earth.

Not all of this will happen without resistance, however; as genomics
seeps into more and more of our daily lives, the tension between scientific
advances and the desire to return to a simple and "more natural" lifestyle
will probably intensify.Francis Collins, MD, PhD,
Director

NATIONAL INSTITUTE ON AGING

The 20th century saw a substantial increase in average human life expectancy,
from 47.3 years to 76.5 years. In the next 20 years, a time when the first
baby boomer turns 65 in 2011, the challenges of an aging population will intensify.
We will make enormous progress in understanding the aging process and in addressing
the diseases that compromise health and function of older people.

The genes that affect longevity, influencing oxidative stress and other
factors, will become better defined, and new insights into the role of telomeres
and the activity of telomerase could lead to improvements in overall health
and gains in the fight against cancer.

Prospects will improve significantly for patients with Alzheimer disease,
as the etiology becomes increasingly evident and new drug treatments, possibly
even preventive measures, become available. Finally, we can all hope that
disability rates among older people will continue to decline.Richard J. Hodes, MD, Director

NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

Prognostication is always a chancy thing. Although one tries to be a
prophet of sorts by extrapolating what is likely to occur in the future from
what is currently known, even the best prophet cannot always predict the inevitable
surprises in science; a "science prophet" making a 50-year prediction in the
1920s would have missed a few "minor details" like penicillin, the fission
of uranium, and DNA! Because there is no reason to think that nature has yet
run out of surprises, my "predictions" admit that the unexpected is likely.

With this caveat in mind, I believe that by the year 2020 the most significant
change in the alcohol field will be a melding of biology and behavior in alcohol
investigations. We are turning in this direction even now with major research
efforts such as our Collaborative Study on the Genetics of Alcoholism, which
involved both biological and behavioral scientists. This melding will be advanced,
I believe, by a rejection of the "reductionist" view, which seeks to define
humankind in terms of its genes, and acceptance of the tenet that genes are
not always (or even mostly) destiny.

Scientifically, I believe that by 2020 we will have discovered at least some of the genes involved in the vulnerability to alcoholism and how genetic
risk is influenced by environmental risk in the development of alcohol-related
problems; we will have identified biological and environmental markers of
risk for alcoholism that will permit us to prevent or intervene in alcohol
problems before they become chronic; we will have developed a range of pharmacotherapies
to treat alcohol dependence based on genetics and neuroscience research; we
will have developed more precise diagnostic tools for alcohol abuse and dependence;
and we will have learned what works best to prevent alcohol problems in specific
populations, such as adolescents, young women, and racial and ethnic minorities.

Most importantly, I believe that by 2020 we will have advanced far beyond
our current grasp of individual neural connections in animals and in humans
to an understanding of how circuits in the brain actually operate in terms
of appetite, affect, and cognition, and that even subjective states, such
as volition and consciousness, will yield to science.Enoch Gordis, MD, Director

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

As we enter the 21st century, there is a growing appreciation of the
importance of global health research. In today's "global village," we cannot
separate the health problems of the United States from those of the rest of
the world.

Increasingly, the powerful new technologies of biomedical science will
be focused on global health and finding new interventions for diseases such
as malaria, tuberculosis, diarrheal diseases, and schistosomiasis, which exact
an enormous burden worldwide.

New therapies and vaccines will likely become available to fight these and other microbial killers. A new generation of combination vaccines will
simplify the current childhood immunization schedule and facilitate the vaccination
of many more of the world's children. Many of our current vaccines will be
replaced by newer vaccine concepts, such as plasmid-based "DNA vaccines."
Plants that carry genes that express vaccine antigens will be used to painlessly
and inexpensively immunize entire populations.

We can also anticipate considerable progress in the fight against HIV and AIDS. In the next two decades, new advances in understanding the host factors and pathogenic mechanisms of HIV disease will help elucidate additional
drug targets in the viral replication cycle and new, less toxic therapeutic
strategies that will allow HIV-infected individuals to lead healthy and productive
lives for extended periods of time. New insights into HIV pathogenesis and
the immune correlates of inhibition of HIV spread within the body, coupled
with advances in vaccinology, will facilitate the development of a vaccine
against HIV that will help slow the HIV pandemic.

Increasingly, many chronic diseases will be shown to have infectious etiologies. This effort will be greatly enhanced by the use of powerful new molecular techniques. The burden of "noninfectious" diseases, such as certain
autoimmune diseases and cardiovascular disease, will be eased by the use of
inexpensive interventions such as antibiotics and vaccines against the causative
microbes.

Researchers also will develop effective ways to block deleterious immune
responses by inducing immune tolerance. These advances will have wide-reaching
ramifications. For instance, the induction of tolerance will help prevent
the rejection of transplanted organs, thereby eliminating the need for lifelong
immunosuppressive therapy for transplant patients. New methods of tolerance
induction also will be used to treat autoimmune diseases such as systemic
lupus erythematosus and type 1 diabetes, as well as asthma and allergies.Anthony S. Fauci, MD, Director

NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

By 2020 we will have stopped immunizing children against polio and measles,
and possibly against Haemophilus influenza type b
and pertussis, because those diseases, like smallpox, will have been eliminated
from the planet. In place of those vaccines, we will be immunizing children
everywhere against Shigella, typhoid fever, pathogenic Escherichia coli, pneumococcus, tuberculosis, and, I hope, HIV.

We will be offering all pregnant women the possibility of a blood test at 7 to 8 weeks' gestation to screen for more than 200 genetic disorders of the fetus, and we may be able to offer in utero or neonatal corrective gene
therapy for many of them. Many physical abnormalities of the developing fetus
will be detected in utero by routine sophisticated scanning, and fetal or
neonatal surgery will be able to correct many of them.

An increasing proportion of physicians' health care time will be spent
helping parents shape the health behaviors of children as preventive measures
against adult disease.

Advances in neuroscience will transform the rehabilitation of patients with brain and spinal cord injury so that full recovery of function will be
possible for many.Duane Alexander, MD, Director

NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

Identification of hearing impairment and other communication disorders
within the first 6 months of life will result in early appropriate intervention
and improved language skill development.

Identification of the genes where mutations result in hereditary hearing impairment in children will revolutionize the diagnosis and treatment of this disorder. At the same time, the possibility of using genetic information
about the status of these genes to make reproductive decisions or choices
about potential marriage partners will raise significant ethical dilemmas.

Variants of the same genes that cause early-onset hereditary hearing
impairment will also be shown to predispose individuals to presbycusis (hearing
loss in older people) and increase the likelihood of noise-induced hearing
loss. Being able to predict which individuals are at increased risk will allow
lifestyle choices to be made that will reduce the likelihood of these hearing
problems.

A vaccine that is effective in preventing otitis media will become
a standard part of childhood immunizations, dramatically reducing the burden
of childhood ear infections.

The molecular mechanisms that govern the development of hair cells in the inner ear will be understood. These cells are responsible for sound
detection and balance, and their loss often underlies hearing impairment and
balance disorders. Understanding the basic mechanisms will lead to treatment
strategies that will regenerate lost hair cells, restoring lost hearing and
ameliorating balance disorders.

Improvements in the function of the cochlear implant will make this device useful for a greatly expanded number of individuals with hearing
impairment. Similar improvements in hearing aids will make these devices much
smaller and more effective.

The molecular mechanisms that allow olfactory neurons to regenerate continuously throughout life will be elucidated and will provide important
clues for stimulating neuronal regeneration in other parts of the nervous
system. These developments will lead to effective treatments for a number
of neurodegenerative disorders.

The genes that determine increased susceptibility to disorders of voice, speech, and language will be elucidated. Knowledge about these genes
and other biomarkers associated with these disorders will improve diagnostic
precision, resulting in optimization of intervention strategies to ameliorate
these disorders.

James F. Battey, Jr, MD, PhD, Director

NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

The first 100 years of the new millennium will be known as the century
of "genes to better quality of life"an era of genomics and functional genomics, bioengineering, innovative imaging, analytical diagnostic assays
with appropriate biomarkers, and aggressive interventions to promote healthone that will be based on integrated partnerships among the public, health care providers, researchers, and educators.

A diverse health care workforce will make this the century of molecular dentistry and medicine aimed at eliminating health disparities. By 2005, the human, mouse, zebrafish, and a large number of more than 100 microbial genomes will be completed. Gene-based diagnostics, preventive interventions, and therapeutics
will soon become "mainstream" dentistry and medicine.

Human complex diseases, such as periodontal diseases, osteoporosis, osteoarthritis, temporomandibular joint disorders, chronic facial pain, dental caries, diabetes, and many others will be assessed and treated based on the
principles of pharmacogenetics, gene-gene and gene-environment interactions,
and health promotion. We anticipate a remarkable infusion of biological and
behavioral solutions to health enhancement.Harold
C. Slavkin, DDS, Director

NATIONAL INSTITUTE ON DRUG ABUSE

We see the future of drug addiction research greatly enhanced by techniques
from a wide variety of scientific disciplines, including advances in molecular
genetic technology and neuroimaging. These technologies will allow researchers
to define the precise anatomical, biochemical, and physiological mechanisms
that determine how the brain works and to pinpoint the mechanisms in the brain
that cause an individual to transition from drug use to drug addiction.

We are also optimistic that advances over the next two decades will
allow us to identify many of the genes that cause an individual to be more
or less vulnerable to drug abuse and addiction. These revolutionary findings
will allow us to not only develop effective prevention programs that are specifically
targeted to populations determined to be most vulnerable to drug use, but
will also allow us to develop treatments that will reverse the brain changes
caused by chronic drug use.Alan I. Leshner, PhD,
Director

NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

The "one-size-fits-all" approach to human risk assessment and the practice
of medicine will be a thing of the past. Researchers in environmental health
sciences and the pharmaceutical industry will have the knowledge base to develop
regulatory policies and medicines most appropriate for specific populations
or individuals, respectively.

The 2-year rodent bioassay for assessing the carcinogenicity of chemicals will no longer be used for this purpose. New test systems, based on new developments
in molecular genetics, will be the standard bearer. Gene expression systems
will transform the way toxicologists approach environmental problems.Kenneth Olden, PhD, Director

NATIONAL INSTITUTE OF MENTAL HEALTH

By 2020 it will be a truth, obvious to all, that mental illnesses are
brain diseases that result from complex gene-environment interactions. We
will be reaping the therapeutic benefits that accrue from the discovery of
risk genes for autism, schizophrenia, manic depressive illness, and other
serious mental disorders.

We will also routinely analyze real-time movies of brain activity derived from functional magnetic resonance imaging, optical imaging, or their successor
technologies, working together with magnetoencephalography or its successor
technology. In these movies, we will see the activity of distributed neural
circuits during diverse examples of normal cognition and emotion; we will
see how things go wrong in mental illness; and we will see normalization with
our improved treatments.Steven E. Hyman, MD, Director

NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

I believe in the next 20 years we will understand much more about every
degenerative disorder affecting the nervous system, and we will have effective
cures for some of them. Neurodegeneration is a ubiquitous phenomenon that
occurs in many brain diseases, not only in the classic neurodegenerative disorders
such as Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis.
Neurodegerative disorders also contribute significantly to epilepsy, multiple
sclerosis, and even depression. Lessons learned in one area will shed light
on all of them.Gerald D. Fischbach, MD, Director

And lessons learned throughout the NIH will surely foster new hope of rosy prospects as the century progresses. Meanwhile, MEDICAL NEWS wishes to thank all those who participated in this visionary exercise, and we wish all our readers a happy and healthy year 2000!